The genome is constantly exposed to DNA damage from endogenous and environmental sources. The DNA damage induced by genotoxic substances can be deleterious and has to be repaired faithfully to maintain genome stability. Cells respond to DNA damage via DNA damage response pathways that activate cell cycle checkpoints and DNA damage repair mechanisms. One major pathway for mending DNA damage induced by endogenous and environmental sources is homologous recombination DNA repair (HR), a highly conserved process that becomes impaired in many human cancers. Canonical HR involves the exchange of genetic material between a pair of identical DNA sequences, allowing for the relatively precise repair of lost sequence information around the damaged DNA site. The HR reaction requires many HR mediator proteins that ensure the efficiency of RAD51 loading and filament stability; key HR mediator proteins include the human breast cancer susceptibility gene products BRCA1, BRCA2, and PALB2. Besides these mediator proteins, a key player that is critical for HR, downstream of RAD51 filament formation, is RAD51-associated protein 1 (RAD51AP1). RAD51AP1 interacts with RAD51 and stimulates RAD51 activity. RAD51AP1 is critical for protecting human cells from the cytotoxic effects of ionizing radiation (IR), DNA cross-linking agents and for replication fork stability. Functional loss of RAD51AP1 leads to impaired HR and to genome instability. Yet, the organismal consequences of RAD51AP1 loss are not understood and have not yet been investigated. Our goal here is to elucidate the phenotype of rad51ap1 knockout mice, both spontaneously and after exposure to IR. This will be the first in-depth investigation of the consequences of Rad51ap1 loss at the whole-animal level. Of importance, rad51ap1 knockout mice are viable and fertile. Wild type, heterozygous and rad51ap1 KO mice will be sham exposed or exposed to 4 Gy total body ?-irradiation and monitored for disease. Once mice appear sick, necropsies will be performed and tissues will be taken for RNA, DNA and histopathology analyses. We expect that Rad51Ap1-deficiency in mice will decrease tumor latency and increase tumor burden after IR exposure, and potentially also under unperturbed/sham conditions. Together, the results from this investigation will shed light on the role of RAD51AP1 for cancer avoidance and tumor suppression. Given the importance of HR in the removal of DNA lesions induced by IR and other environmental mutagens, the knowledge produced will have direct relevance to risk predictions for health from environmental factors.